Parkinson's Disease (PD) is a devastating neurodegenerative disorder that affects approximately 500,000 people in the US and an additional 50,000 are diagnosed each year. This disease is characterized by tremors in the limbs, bradykinesia, akinesia, rigid limbs, and a shuffling gait. The symptoms of PD are caused by the destruction of dopaminergic neurons in the substantia nigra, leading to a severe reduction in dopamine concentrations within the brain. PD treatment is currently more like a common cold, with drugs that alleviate symptoms but do not address the underlying cause of the disease. Unfortunately, this approach does nothing to reduce neurodegeneration of dopaminergic neurons such that the severity of PD increases. Any new treatment that provides neuroprotection and eliminates neurodegeneration would provide a fundamental improvement over current treatments. Recent research indicates that inflammation plays a significant role in development of PD. In addition, there are a number of reports that characterize genetic factors that influence the disease progression and incidence. The protein apolipoprotein E (ApoE) provides a convergence point for these factors. Several reports implicate the e4 allele of ApoE as playing a critical role in the age of onset for development of PD. In addition, ApoE has been shown to have significant anti-inflammatory effects within the brain. Cognosci Inc. has investigated the anti-inflammatory effects of ApoE for several years and have documented some of the mechanisms of anti-inflammatory and neuroprotective effects of ApoE and derivatives. These investigations have lead to isolation of an anti-inflammatory/neuroprotective peptide, COG133, that may be an effective therapeutic for neurodegenerative disease. In this proposal, we will test COG133 for treatment of PD via a novel mechanism. This approach to PD therapeutics represents a paradigm shift in the development of PD therapeutics. The goal of the proposed project entitled "Novel Therapy for Parkinson's Disease" is to evaluate a novel approach to treatment of a debilitating disease that presently affects over 500,000 predominantly elderly Americans. Advances made through the proposed project could lead to new therapies that reduce the debilitating effects of the disease and lessen the burden on society in caring for those who cannot care for themselves. Success in development of new therapeutics will also provide for a potentially significant increase in quality of life for affected patients and their families. [unreadable] [unreadable] [unreadable]